Moderate to severe hemophilia B

For one-time single-dose intravenous infusion only.

For patient selection

Perform testing for pre-existing neutralizing antibodies to AAVRh74var using an approved companion diagnostic. DO NOT administer fidanacogene elaparvovec to patients with a positive test for antibodies to AAVRh74var.

• Perform factor IX (FIX) inhibitor testing prior to infusion. DO NOT administer fidanacogene elaparvovec to patients with a positive test (≥0.6 Bethesda Units [BU]) or a prior history for factor IX inhibitor.
• Perform HIV testing prior to infusion. DO NOT administer fidanacogene elaparvovec to patients with either CD4+ cell count <200 mm³ or viral load ≥20 copies/mL in case of serological evidence of HIV-1 or HIV-2 infection.
• DO NOT administer fidanacogene elaparvovec to patients with hypersensitivity to factor IX replacement product.
• Perform liver health assessments, which include:
  • Liver function tests (alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase [ALP], bilirubin, albumin).
  • Laboratory tests for active hepatitis B or C.
  • Elastography and/or ultrasound and other laboratory assessments for liver fibrosis.

Dose

The recommended dose of fidanacogene elaparvovec is a single-dose intravenous infusion of 5 × 10¹¹ vector genomes per kg (vg/kg) of body weight.

To determine the patient’s required dose, the following calculation step is needed:

Calculation of patient’s dose weight

The dosing of fidanacogene elaparvovec is based on the patient’s body mass index (BMI) in kg/m².

Monitoring post-administration

Conduct the following laboratory tests after administration of fidanacogene elaparvovec:

• Perform ALT, AST as in Table 1 to monitor for liver enzyme elevation which may indicate immunemediated hepatotoxicity. Liver enzyme elevation may result in decrease in factor IX activity. Perform factor IX activity testing as shown in Table 1.
• In patients with elevated transaminases and/or decline in factor IX activity, continue monitoring transaminases and factor IX activity until transaminases return to baseline and/or factor IX activity has plateaued.

Table 1. Recommended Hepatic Function (ALT and AST) and Factor IX Activity Monitoring:

It is recommended where possible to use the same laboratory facility for monitoring over time, particularly during the timeframe for corticosteroid treatment decision making, to minimize inter-laboratory variability.
^* Starting at Week 65.

• Consider implementing a course of corticosteroids as outlined in Table 2 for any of the following:
  • Single increase in either ALT or AST of ≥1.5-fold from baseline after screening and prior to infusion even if within the normal range.
  • Consecutive increases in transaminases (ALT or AST or both) on 2 subsequent blood tests even if within the normal range.
  • Factor IX activity decrease
    • In the absence of alternative etiology, a decrease that could trigger the risk of bleeding.
    • A decrease in factor IX activity on 2 consecutive blood tests especially if occurring during the first 4 months post-infusion.
• The recommended starting dose of oral corticosteroids is 60 to 100 mg once a day. Start to taper prednisolone/prednisone when the ALT and/or AST have declined for at least 2 consecutive lab draws and/or the levels have begun to normalize and any decline in factor IX activity has plateaued.
• Monitor for and manage adverse reactions secondary to corticosteroid use. Refer to the corticosteroid prescribing information for risks and required precautions.

Table 2. Recommended treatment regimen for oral corticosteroids:

^* Based on body weight.
^** See the paragraph below this table.
^*** Maintain at 20 mg/day until transaminases return to baseline, then reduce by 5 mg/day until 10 mg/day are achieved then reduce by 2.5 mg/week up to 5 mg daily.

If there is persistent transaminase elevation while on oral corticosteroids treatment alone, consult with a hepatologist as required to discuss use of combined oral and intravenous corticosteroids (methylprednisolone).

• Monitor Factor IX Activity.
  • Monitor factor IX activity levels according to Table 1 to confirm adequate endogenous FIX activity levels to support discontinuation of pre-infusion FIX prophylaxis therapy. In the clinical studies, a prophylactic dose of factor IX replacement was given prior to fidanacogene elaparvovec infusion and following that, patients discontinued prophylaxis. Exogenous factor IX or other hemostatic products may also be required in case of surgery, invasive procedures, trauma, or bleeds in the event that fidanacogene elaparvovec-derived factor IX activity is deemed insufficient for adequate hemostasis in such situations.
  • The use of different assays may impact test results; therefore, use the same assay and reagents to monitor patients over time, if feasible.
  • Use of exogenous FIX concentrates before and after fidanacogene elaparvovec administration may impede assessment of endogenous, fidanacogene elaparvovec-derived factor IX activity.
• Monitor patients for factor IX inhibitors (neutralizing antibodies to factor IX). Test for factor IX inhibitors especially if bleeding is not controlled, or plasma factor IX activity levels decrease.
• Perform regular liver ultrasound (e.g., annually) and alpha-fetoprotein (AFP) testing in patients with risk factors of hepatocellular carcinoma (e.g., hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, advanced age).